Discovery of a New Series of Naphthamides as Potent VEGFR-2 Kinase Inhibitors
Discovery of a New Series of Naphthamides as Potent VEGFR-2 Kinase Inhibitors
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发现一系列新萘酰胺作为有效的 VEGFR-2 激酶抑制剂
DOI：
10.1021/ml5000417
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发表时间：
2014-05-01
影响因子：
4.2
通讯作者：
Duan, Wenhu
中科院分区：
文献类型：
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作者：
Lv, Yongcong;Li, Mengyuan;Duan, Wenhu
抑制VEGFR-2信号通路已经成为治疗癌症最有前途的方法之一。在这项研究中，我们描述了一系列新的萘酰胺作为VEGFR-2的有效抑制剂的设计、合成和生物学评价。在这些化合物中，14c在酶促和HUVEC细胞增殖试验中均表现出较高的VEGFR-2抑制效力，IC50值分别为1.5和0.9 nM。激酶选择性分析显示，14c是一种多靶点抑制剂，对VEGFR-1、pdgfr - β和RET也表现出良好的效力。此外，14c在纳摩尔水平上有效地阻断HUVEC的管状形成。总的来说，14c可能是治疗癌症的一个有希望的候选者。
Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer. In this study, we describe the design, synthesis, and biological evaluation of a new series of naphthamides as potent inhibitors of VEGFR-2. Among these compounds, 14c exhibited high VEGFR-2 inhibitory potency in both enzymatic and HUVEC cellular proliferation assays, with IC50 values of 1.5 and 0.9 nM, respectively. Kinase selectivity profiling revealed that 14c was a multitargeted inhibitor, and it also exhibited good potency against VEGFR-1, PDGFR-beta, and RET. Furthermore, 14c effectively blocked tube formation of HUVEC at nanomolar level. Overall, 14c might be a promising candidate for the treatment of cancer.